Interactions between the mGluR2/3 agonist, LY379268, and cocaine on in vivo neurochemistry and behavior in squirrel monkeys

• Type of Material: Article
• Authors: Rayna M. Bauzo, Emory University; Heather Kimmel, Emory University; Leonard Howell, Emory University
• Language: English
• Date: 2009-11
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.crossref.org/10.1016%2Fj.pbb.2009.08.011
• Title of Journal or Parent Work: Pharmacology Biochemistry and Behavior
• ISSN: 0091-3057
• Volume: 94
• Issue: 1
• Start Page: 204
• End Page: 210
• Research Categories: Health Sciences, Pharmacology; Chemistry, Biochemistry

Abstract

Recent evidence indicates that group II metabotropic glutamate receptors (mGluR2 and mGluR3) may play a role in the pathology of cocaine addiction. The purpose of the current study was to determine the effects of the mGluR2/3 agonist, LY379268, on cocaine-induced changes in DA neurochemistry in nonhuman primates. Furthermore, the current study aimed to determine if changes in DA neurochemistry would correlate with LY379268-induced changes in the behavioral effects of cocaine. In vivo microdialysis was conducted in conscious squirrel monkeys (n=4) in order to monitor cocaine-induced changes in extracellular DA in the caudate nucleus. Separate groups of subjects were trained on a fixed-interval schedule of stimulus termination (n=4) or a second-order schedule of cocaine self-administration (n=5) to characterize the behavioral-stimulant and reinforcing effects, respectively. LY379268 significantly attenuated cocaine-induced increases in DA. LY379268 also significantly attenuated cocaine-induced behavioral-stimulant effects following a short pretreatment time, but not following a longer pretreatment time. Cocaine self-administration was significantly attenuated but only at an intermediate pretreatment dose of LY379268. Moreover, reinstatement of previously extinguished cocaine self-administration was not significantly attenuated by LY379268. Hence, drug interactions on neurochemistry did not correlate well with behavioral measures.